Single administration of thrombopoietin prevents progression of liver fibrosis and promotes liver regeneration after partial hepatectomy in cirrhotic rats.
OBJECTIVE
To evaluate the effect of thrombopoietin on liver regeneration after hepatectomy and antifibrosis under conditions of liver cirrhosis in rats.


BACKGROUND
We revealed that platelets induced by thrombopoietin administration promote liver regeneration after hepatectomy in the normal liver.


METHODS
Seventy percent hepatectomy was carried out in rats, which were subsequently divided into 4 groups: (1) normal group without any treatment, (2) liver cirrhosis (LC) group, (3) combined thrombopoietin and liver cirrhosis (LC+TPO) group, and (4) combined thrombopoietin, antiplatelet serum and liver cirrhosis (LC+TPO+APS) group. Growth kinetics in the liver regeneration and growth factors were analyzed. Liver fibrotic area and activation of hepatic stellate cells were also investigated.


RESULTS
In LC group, liver regeneration was significantly delayed compared with normal group 24 hours after hepatectomy. On the other hand, liver regeneration of LC+TPO group increased significantly compared with LC group, to a level that was the same as that recorded in normal group. In LC group, liver fibrotic area before hepatectomy was significantly higher compared with the normal group. Liver fibrosis of LC+TPO group was significantly reduced compared with LC group. The antifibrotic and liver regeneration promoting effects of LC+TPO group were inhibited by antiplatelet serum in LC+TPO+APS group.


CONCLUSIONS
The administration of thrombopoietin reduces liver fibrosis and stimulates regeneration after hepatectomy through increment and accumulation of platelets in the cirrhotic liver. This could be a potentially useful treatment for liver cirrhosis.
Murata
Soichiro
S
Department of Surgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
Hashimoto
Ikuka
I
Nakano
Yoritaka
Y
Myronovych
Andriy
A
Watanabe
Motonobu
M
Ohkohchi
Nobuhiro
N
D000818:Animals; D018450:Disease Progression; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000503:physiopathology* / Q000517:prevention & control*; D017093:Liver Failure / Q000517:prevention & control; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011183:Postoperative Complications / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D013926:Thrombopoietin / Q000008:administration & dosage*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I; D013926:Thrombopoietin